Dμ expression causes enrichment of MZ B cells, but is non permissive for B cell maturation in Rag2−/− mice even if combined with Bcl-2

Rearrangements in reading frame 2 promote the expression of a truncated heavy chain, the Dμ protein. Dμ can assemble into a pre-B cell receptor like complex that appears to induce a subset of signals elicited by full length μ, but cannot promote the pro-B to pre-B cell transition of Rag−/− B cells. In order to determine if this could stem from an impaired survival signal not properly induced by the Dμ protein, we introduced Bcl-2 into Dμ-transgenic, Rag2−/− mice. Despite the fact that the Bcl-2 transgene expression promoted some increase in the fraction of CD43− B cells, an identical increase was also observed in Rag2−/− mice. Moreover, whereas in μ-transgenic Rag2−/−Bcl-2+ mice, CD2 and CD25 expression were up regulated and c-Kit was down regulated, these markers were unaltered in Dμ-transgenic Rag2−/− Bcl-2+ mice compared to Rag2−/− Bcl-2+ mice, indicating that Dμ cannot support pre-B cell maturation despite extended survival of B cell precursors by Bcl-2. In addition, we observed that in Dμ-transgenic recombination competent mice, the Dμ induced partial block is permissive for marginal zone B cell development whereas the formation of follicular B cells is severely reduced. While the Dμ protein is expressed in peripheral B cells escaping the block, only a minor fraction of Dμ is exposed to the outer cell surface.